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Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model

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Abstract

Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8 mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1β (IL-1β), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced Aβ1–42 protein accumulation in brain of mice. Remarkably CNM’s effect on IL-1β was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden.

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Acknowledgements

The authors are grateful for Dr. Nouran Elshehaby who generously provided the Aβ1–42 antibody and Dr. Asmaa Khairy who helped with immunohistochemistry analysis.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, MSA University, Cairo, Egypt

    Doaa Abou El-ezz & Amany El-brairy

  2. Department of Biochemistry, Faculty of Pharmacy, MSA University, Cairo, Egypt

    Ahmed Maher

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Nada Sallam & Sanaa Kenawy

  4. Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Nada Sallam

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  1. Doaa Abou El-ezz
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Correspondence to Doaa Abou El-ezz or Ahmed Maher.

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Abou El-ezz, D., Maher, A., Sallam, N. et al. Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model. Neurochem Res 43, 2333–2342 (2018). https://doi.org/10.1007/s11064-018-2656-y

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